1. Cytokines and Chemokines Chapter 12 Karl A. Brokstad 1

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4. Cytokines - Nomenclature Monokines Lymphokines Cytokines (generic term) interleukins 4

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7. Cytokine actions Development of cellular and humoral immune responses Induction of inflammation Regulation of hematopoiesis Control of cellular proliferation and differentiation Induction of wound healing Chemotaxis 7

8. Main classes of cytokines Interleukins (IL) Interferons (IFN) Chemokines (CXC, CC, C, CX3C) Colony stimulating factors (CSF) Tumor necrosis factors (TNF) 8

9. properties Antagonistic Synergistic Redundancy Pleiotropism Cascade action 9

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14. Figure 8-32 14

15. Cytokine receptors Type I cytokine receptors Type II cytokine receptors IL-1 family receptors TNF receptor Chemokine receptors 15

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27. Inflammation Function 1.Deliver effector cells 2.Construct barrier 3.Repair damage Stages 1.Recognise pathogen/damage 2.Express signalling molecules 3.Increase vascular diameter, higher flow, lower velocity 4.Vascular permeability 5.Clothing microvessels IL1, IL6, TNF- , INF- , IFN- , IFN-  IL-8 27

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29. Figure 2-15 29

30. Figure 2-39 30

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32. Figure 2-48 32

33. Pro-inflammatory: IL-1, IL-6, TNF- , IL-12, IL-18, (IFN- , chemokines) Anti-inflammatory: IL-4, IL-10, IL-13, TGF-  Inflammatory cytokines 33

34. Chemokines Migration factors 34

35. Figure 2-41 part 1 of 2 35

36. Figure 2-41 part 2 of 2 36

37. Th1: IL-2, IFN-  Th2: IL-4, IL-5, IL-13 Th3/Tr: IL-10, TGF-  Th17: IL-17 Th1-3 Cytokines 37

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40. 40 TH0TH0TH1TH1TH3TH3 IL-2, IFN- , TNF-  IL-4, IL-5, IL-6, IL-10, IL-13 TGF- , IL-10 TH2TH2 IFN-  IL-4, IL-10 NK M IL-12, IFN- , IL-18 MAST IL-4 NK M TCTC CD4+ T helper cells TR1TR1 CD4+ CD25+ FOXP3+ Cellular immunity Humoral immunity B IL-4 IFN-  T H 17 IL-17 Inflammation Regulatory actions anti-inflammation TGF- , IL-6, IL- 1 IL-23

41. BBB IgMIgE / IgG1IgA / IgG2bIgG2a / IgG3 Proliferation cytokines IL-2, IL-4, IL5 IL-4 TGF-  IFN-  Diffentiating cytokines 41

42. Functional categories Mediate/regulate innate immunity –TNF, IL-1, IL-12, IFN type1, IL-10 Mediate/regulate adaptive immunity –IL-2, IL-4/13, IFN-γ, TGF-β Stimulates hematopoiesis – development / differetiation / maturation –IL-3, IL-7 42

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44. TNF Innate immunity Acute inflammation Produced by monocytes/macrophages 44

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48. IL-1 Innate immunity Acute inflammation fever 48 IL-1α IL-1RA sIL-1R IL-1R IL-1β

49. 49 IL-12 Innate immunity Cell mediated immunity MØ, act.DC Th1  IFN-gamma

50. 50 IFN-α + IFN-β (type 1 IFN) Produced by virusinfected cells TLR-3, 7, 9

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52. 52 IL-2 growth, survival, differentiation factor

53. 53 IL-4 (+IL-13) IgE + parasites

54. 54 IFN-γ

55. Hematopoiesis IL-3  myeolid cells IL-7  lymphoid cells 55

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59. cell cytoplasm nucleus stimulation /activation Signal transduction pathway transcription (mRNA) translation (pre-cytokine) secretion (cytokine) measure directly in body fluids e.g. ELISA measure intracellular e.g. Flow Cytometry measure expression levels e.g. Q-PCR EFFECT DETECTION 59